GHRH-deleted Mice Are Severely Deficient in Vaccine And Immunological Responses Against Streptococcus Pneumoniae

Background and objective of the work.
Ghrh-/- mice with a severe deficiency of their somatotrope GHRH/GH/IGF1 axis (1) are resistant to experimental allergic encephalomyelitis (2). In basal conditions, thymus and T-cell development are not severely affected but a marked spleen atrophy and B-cell lymphopenia were constantly observed (3). Therefore, we investigated vaccinal and anti-infectious responses of Ghrh-/- mice against S.pneumoniae, a T-independent pathogen.
Results.
Transgenic mice were unable to trigger production of specific IgM after vaccination with either native pneumococcal polysaccharides (PPS, Pnx23) or protein-PPS conjugate (Prev13). GH treatment of Ghrh-/- mice restored IgM response to Pnx23 vaccine but not to Prev13 suggesting that GH exerts a significant impact on the spleen marginal zone that is strongly implicated in T-independent immunological response to pneumococcal polysaccharides.
After intranasal instillation of a non-lethal dose of S.pneumoniae, Ghrh-/- mice exhibited a dramatic susceptibility with a time-dependent increase in lung bacterial load, a bacteremia already after 24h, and a survival limit of 48-72h. In marked contrast, WT and heterozygote mice completely cleared S.pneumoniae infection after 24h. Lungs of infected Ghrh-/- mice were massively infiltrated by inflammatory macrophages, while lung B cells were markedly decreased. Transcription of Ifng, Il10, Cd40, and Cxcl9 was highly increased in the lungs of infected Ghrh-/- mice, whereas Tgfb and Iggj transcripts were unchanged.
Resistance of Ghrh-/- mice to infection by influenzavirus H1N1 (a T-dependent antigen) was normal or slightly decreased.
Conclusion.
This animal model shows that the somatotrope GHRH/GH/IGF1 axis plays a vital and unsuspected role in the vaccine and immunological defense against S.pneumoniae.